Voices of Impact – Prof. Yosef Yarden

Established by Susan G. Komen for the Cure® in 1992, the Brinker Award for Scientific Distinction is a marquee award that honors leading scientists for their significant achievements and contributions in basic and translational science and clinical practice that have advanced the fight to save lives and realize our vision of a world without breast cancer. This year’s awardees are Dr. Hyman Muss, an American clinician-scientist and Prof. Yosef Yarden, an Israeli researcher whose work has led to more personalized treatments for breast cancer. Dr. Muss and Prof. Yarden received their awards at the 2012 San Antonio Breast Cancer Symposium on December 5, 2012.

YOSEF YARDEN, Ph.D., Rehovot, IsraelProfessor of Molecular Biology at the Weizmann Institute of Science; Head of the Marvin Tanner Laboratory for Research on Cancer; Incumbent of the Harold and Zelda Goldenberg Professorial Chair in Molecular Cell Biology; Research Professor, Israel Cancer Research Fund

“I was driven by curiosity—what causes cells to grow and how do these processes go awry in cancer? —and the challenge of answering these questions through research.”

Cancer biology is like a very complicated puzzle, and scientific discoveries are like the puzzle pieces that fit together to help us see the full picture, to help us understand the biological drivers of cancer and how we can target them with cancer drugs. I am especially proud that my basic research has helped put together some pieces of the breast cancer puzzle and build the foundation for several widely used breast cancer drugs that target key molecules driving breast cancer.

But when I first joined the field, my initial motivation was scientific. I was driven by curiosity—what causes cells to grow and how do these processes go awry in cancer? —and the challenge of answering these questions through research. At this time, we did not know that epidermal growth factor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) are related to so many types of tumors. The term “HER2-positive” breast cancer did not exist.

As an undergraduate student at the Hebrew University in Jerusalem, my enthusiasm was ignited by the ability of small biologically active molecules, called growth factors, to cause certain cells to respond (for example, by growing and dividing) while not affecting neighboring cells. I was fascinated by studies reported by Stanley Cohen, who found that a specific receptor, or protein on the cell surface, could bind to epidermal growth factor (EGF) and trigger a cell to respond. Hence, my doctoral project at the Weizmann Institute focused on the receptor for EGF (called EGFR). This work led to two important discoveries: the one that received media coverage found that a large portion of the genetic code for EGFR was included in a virus, which causes cancer in birds. Unexpectedly, the other finding revealed that EGFR is inactive unless it forms a pair with another EGFR molecule.

By the time I was polishing my thesis, a protein in the same family as EGFR was independently discovered by Axel Ullrich (who called it HER2) and Robert Weinberg (who called it Neu). Later studies by Dennis Slamon and others reported exaggerated levels of HER2/Neu in breast tumors. The puzzle begins to take shape.

I went on to train in Ullrich’s and Weinberg’s laboratories (1985-1989). While there and later in my own laboratory in Rehovot, we extensively compared EGFR and HER2/Neu. These studies, some of which were generously supported by Susan G. Komen for the Cure, discovered the Neuregulin family of EGF-like factors and led to the realization that HER2/Neu regulates a network of receptors. In other words, by forming pairs with EGFR and other family members, HER2/Neu enhances and prolongs biochemical signals initiated by growth factors in the neuregulin family and EGF. Hence, blocking HER2/Neu in breast cancer with targeted drugs can block the action of multiple growth factors and receptors, thereby inhibiting tumor growth.

Decades of research have helped us to understand the biology of breast cancer and apply that knowledge to develop better ways to treat breast cancer, based on the proteins driving the growth and spread of tumor cells. But the puzzle is not complete. Our current studies are unveiling a plethora of molecular mechanisms that permit HER2/Neu to evade processes inside the cell, like intracellular breakdown of HER2/neu, that regulate its activity. Understanding how HER2/neu is regulated will help us to develop new ways to enhance the therapeutic impact of anti-HER2/neu drugs.

I’m honored to be recognized for my contributions to this understanding of breast cancer biology with the Brinker Award for Scientific Distinction, but clearly, no single researcher or scientist holds all of the answers, and I am grateful for the community of global researchers working together to unlock the pieces of cancer’s puzzles. By funding research in the U.S. and internationally, I see Susan G. Komen for the Cure as a convener of the global research community – a vital step toward Komen’s noble goal of ending suffering from breast cancer forever.

About the author

Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen and launched the global breast cancer movement. Today, Komen is the world’s largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Thanks to events like the Komen Race for the Cure®, we have invested more than $1.9 billion to fulfill our promise, becoming the largest source of nonprofit funds dedicated to the fight against breast cancer in the world.